As part of an ongoing program examining the regulation of cyclic AMP accumulation in brain tissue, the current project is focused on the study of mechanisms responsible for potentiative interaction between pairs of agonists. In the most extreme examples of this phenomenum, observed in slices of fetal guinea pig cerebral cortex, one member of the pair (e.g., gamma-adrenergic agonists, glutamate) produces no visible change in cyclic AMP accumulation in the absence of the other (e.g., histamine, adenosine). It is proposed to follow up observations that treatment of tissue with glutaraldehyde produces cross-linking of about 25% of the total cyclic AMP to insoluble cell constituents and to develop immunohistochemical and/or radioautographic procedures for the localization of changes in cyclic AMP metabolism. One important question to be asked in the initial applications of these procedures is whether a given cell type requires the presence of two agonists in order to accumulate detectable amounts of cyclic AMP.